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本研究总结成人Ph染色体和/或BCR-ABL融合基因阳性的混合表型急性白血病(Ph+MPAL)患者的临床和实验室特征。回顾性分析2009年1月-2012年9月在我院诊治的15例Ph+MPAL的特征及细胞形态学、免疫学、细胞遗传学和分子生物学检测以及临床随访结果。Ph+MPAL的诊断采用WHO-2008分类标准。结果表明,Ph+在同时期总MPAL群体中的检出率为17.2%(15/87)。15例患者中男性7例、女性8例;中位年龄为51(16-81)岁;初诊时中位WBC计数为69(12.7-921)×109/L。形态学检查显示为急性髓系白血病(AML)者2例(13.3%),急性淋巴细胞白血病(ALL)者6例(40.0%)、杂合型白血病(HAL)者7例(46.7%)。免疫学分析表明,此15例患者均为B淋系和髓系混合表达,93.3%患者的白血病细胞表面有CD34的表达,其中64.3%(9/14)的患者CD34表达率在60%以上。染色体R显带技术检测显示,正常核型者2例(13.3%),单纯Ph+者8例(53.3%),Ph+伴附加异常者5例(33.3%)。附加的染色体异常分别为-7(2例)、+Ph(1例)、dic(7;9)(1例)、i(8q)和-16(1例);有残余正常分裂相者4例。多重巢式PCR检测发现,e1a2型融合基因6例(40.0%)、b2a2或b3a2型共9例(60.0%)。7例Ph+MPAL患者中有4例检测到IKZF1基因缺失。本组中10例患者诱导治疗一疗程后完全缓解(CR)率为70.0%,其中联合酪氨酸激酶抑制剂(TKI)组的CR率(83.3%;5/6),优于单纯化疗组(50.0%;2/4),但差异无统计学意义(P>0.05)。随访至今,6例患者由于疾病复发或进展而死亡(60.0%;6/10)。异基因造血干细胞移植(allo-HSCT)组患者总生存优于单纯化疗组(P=0.004)。结论:Ph+MPAL主要为B淋系和髓系混合表达,多数年龄较大,高表达CD34抗原。在BCR-ABL融合基因亚型和基因突变方面类似于Ph+急性白血病。初诊时WBC计数是独立的预后因素,复发进展仍是此类患者死亡的主要原因。联合TKI和allo-HSCT或许能改善预后,有必要进行前瞻性、多中心的临床试验来验证。
This study summarizes the clinical and laboratory characteristics of patients with mixed-phenotype acute leukemia (Ph + MPAL) who have positive Ph chromosome and / or BCR-ABL fusion gene. The characteristics of Ph + MPAL in 15 cases diagnosed and treated in our hospital from January 2009 to September 2012 were analyzed retrospectively. The results of cell morphology, immunology, cytogenetics and molecular biology and clinical follow-up were also analyzed. Ph + MPAL diagnosis using WHO-2008 classification criteria. The results showed that the detection rate of Ph + in the total MPAL population of the same period was 17.2% (15/87). Seven of 15 patients were male and 8 were female; the median age was 51 (16-81) years; median WBC count was 69 (12.7-921) x 109 / L at first visit. Morphological examination revealed 2 cases (13.3%) of acute myeloid leukemia (AML), 6 cases (40.0%) of acute lymphoblastic leukemia (ALL) and 7 cases (46.7%) of heterozygous leukemia (HAL). Immunological analysis showed that all 15 cases were mixed with B lymphoid cells and myeloid cells. The expression of CD34 on the surface of leukemia cells in 93.3% of the patients, of which 64.3% (9/14) were over 60%. Chromosome R banding technique showed that there were 2 cases (13.3%) with normal karyotype, 8 cases (53.3%) with Ph + alone, and 5 cases (33.3%) with Ph + abnormalities. Additional chromosomal abnormalities were -7 (2), + Ph (1), dic (7; 9) (1), i (8q) and -16 example. Multiple nested PCR showed that e1a2 fusion gene was found in 6 cases (40.0%) and b2a2 or b3a2 in 9 cases (60.0%). IKZF1 gene deletion was detected in 4 of 7 Ph + MPAL patients. In this group, the complete remission (CR) rate was 70.0% in 10 patients after one course of induction therapy. The CR rate (83.3%; 5/6) in combination with tyrosine kinase inhibitor (TKI) group was better than that in chemotherapy alone group (50.0%; 2/4), but the difference was not statistically significant (P> 0.05). Up to now, 6 patients died of recurrence or progression of the disease (60.0%; 6/10). The overall survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) group was better than that of chemotherapy alone group (P = 0.004). Conclusion: Ph + MPAL is predominantly B lymphoid and myeloid mixed expression, most of which are older and have high expression of CD34 antigen. Similar to Ph + acute leukemia in BCR-ABL fusion gene subtypes and gene mutations. WBC count at initial diagnosis is an independent prognostic factor and the progression of relapse is still the leading cause of death in such patients. Combined with TKI and allo-HSCT may improve the prognosis, it is necessary to carry out prospective, multicenter clinical trials to verify.